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Updated: May 24, 2025
A Tuberculosis Molecular Bacterial Load Assay TB-MBLA
Published on: April 30, 2020
Cell-free DNA next-generation sequencing for Mycobacterium tuberculosis obtained from plasma of children with active
Shuting Quan1, Xue Tian1, Yuting Sun1
1Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing Key Laboratory of Core Technologies for the Prevention and Treatment of Emerging Infectious Diseases in Children, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Center for Children's Health, Beijing, China.
Background:
Difficulties in microbiologically confirming childhood tuberculosis (TB) can result in delayed treatment and increased disease severity.
Methods:
In this study, we for the first time used whole genome next-generation sequencing (NGS) to detect cell-free DNA (cfDNA) from Mycobacterium tuberculosis (MTB) in plasma from children.
Results:
We enrolled 94 children with active TB and 32 children with other respiratory infections. Combining NGS with probe capture enrichment (targeted cfNGS) showed higher coverage and detecting capability than did NGS alone. The targeted cfNGS showed slightly lower sensitivity (31.9% vs. 44.7%, P = 0.072) and specificity (96.9% vs. 100.0%, P = 0.236) to those of sputum tested using Xpert. Agreement between cfNGS-plasma and Xpert-sputum was weak (κ = 0.217). Concordant results were obtained for only 85 children (67.5%; 16 cases positive by both tests and 69 cases negative by both tests). A total of 40 children with MTB culture negative results were tested to have positive cfNGS-plasma or Xpert-sputum outcomes, yielding a significantly increased percentage of children with bacteriological evidence (20.2% [19/94] for MTB culture-positive only vs. 62.8% [59/94] for cfNGS-plasma, Xpert-sputum or culture positive).
Conclusions:
These data suggest that cfNGS performed well for diagnosing TB using plasma from children. cfNGS may be a new method for diagnosing patients with paucibacillary TB.
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